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标题: 牛磺胆酸通过削弱CD8 + T和NK细胞功能来抑制HBeAg阳性慢性乙型 [打印本页]

作者: StephenW    时间: 2021-1-15 13:11     标题: 牛磺胆酸通过削弱CD8 + T和NK细胞功能来抑制HBeAg阳性慢性乙型

Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8 + T and NK cell function
Zhen Xun  1   2   3 , Jinpiao Lin  1   2   3 , Qingqing Yu  3 , Can Liu  1   2   3 , Jinlan Huang  1   2   3 , Hongyan Shang  1   2 , Jianhui Guo  1   2 , Yuchen Ye  3 , Wennan Wu  1   2 , Yongbin Zeng  1   2 , Songhang Wu  1   2 , Siyi Xu  1   2 , Tianbin Chen  1   2   3 , Jing Chen  4 , Qishui Ou  5   6   7
Affiliations
Affiliations

    1
    Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
    2
    Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
    3
    First Clinical College, Fujian Medical University, Fuzhou, China.
    4
    Center of Liver Diseases, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
    5
    Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China. [email protected].
    6
    Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China. [email protected].
    7
    First Clinical College, Fujian Medical University, Fuzhou, China. [email protected].

    PMID: 33432062 DOI: 10.1038/s41423-020-00601-8

Abstract

Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNα therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-γ, TNF-α, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3+CD8+ T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3+CD8+ T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-α in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNα therapy by impairing the effector functions of CD3+CD8+ T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-α responsiveness during CHB treatment.

Keywords: Bile acids; Hepatitis B virus; Immune cells; Mechanism; Pegylated interferon.

作者: StephenW    时间: 2021-1-15 13:11

牛磺胆酸通过削弱CD8 + T和NK细胞功能来抑制HBeAg阳性慢性乙型肝炎患者对干扰素-α治疗的反应
甄勋1 2 3,林金彪1 2 3,余庆清3,刘残1 2 3,黄金兰1 2 3,商红岩1 2,郭建辉1 2,雨辰叶3,吴文南1 2,曾永斌1 2,吴松航1 2,徐思怡1 2,陈天斌1 2 3,陈静4,Qi水5 6 7
隶属关系
隶属关系

    1个
    福建医科大学附属第一医院基因诊断研究中心检验医学科,福州。
    2
    福建医科大学附属第一医院福建省检验医学重点实验室,福州。
    3
    福建医科大学第一临床学院,福州。
    4
    福建医科大学附属第一医院肝病中心,福州。
    5
    福建医科大学附属第一医院基因诊断研究中心检验医学科,福州。 [email protected]
    6
    福建医科大学附属第一医院福建省检验医学重点实验室,福州。 [email protected]
    7
    福建医科大学第一临床学院,福州。 [email protected]

    PMID:33432062 DOI:10.1038 / s41423-020-00601-8

抽象

聚乙二醇化干扰素-α(PegIFNα)治疗对乙型肝炎电子抗原(HBeAg)阳性的慢性乙型肝炎(CHB)患者的疗效有限。但是,对该故障的根本机制了解甚少。我们旨在调查胆汁酸(BAs),特别是牛磺胆酸(TCA)对CHB患者对PegIFNα治疗的反应的影响。在这里,我们使用质谱法确定了110例慢性HBV感染患者和20例健康对照(HCs)的血清BA谱。我们发现,与HCs和其他慢性HBV感染阶段的患者相比,HBeAg阳性CHB患者的血清BAs,尤其是TCA显着升高。此外,血清BAs,特别是TCA,抑制了HBeAg阳性CHB患者对PegIFNα治疗的反应。从机制上讲,使用流式细胞仪测量IFN-γ,TNF-α,颗粒酶B和穿孔素的表达水平,以评估低或高BA水平患者免疫细胞的效应子功能。我们发现BAs减少了HBeAg阳性CHB患者的CD3 + CD8 + T细胞和自然杀伤(NK)细胞的数量和比例,并削弱了其效应功能。 TCA尤其在体外和体内降低了CD3 + CD8 + T和NK细胞的频率并削弱了其效应功能,并在体外抑制了IFN-α的免疫调节活性。因此,我们的结果表明,BAs,尤其是TCA,通过削弱HBeAg阳性CHB患者的CD3 + CD8 + T和NK细胞的效应子功能来抑制对PegIFNα治疗的反应。我们的研究结果表明,靶向TCA可能是恢复CHB治疗过程中IFN-α反应性的有前途的方法。

关键字:胆汁酸;乙型肝炎病毒;免疫细胞;机制;聚乙二醇化干扰素。
作者: StephenW    时间: 2021-1-15 13:11

https://www.nature.com/articles/s41423-020-00601-8
作者: ybdn    时间: 2021-1-18 07:17

肝脏中牛磺酸的作用是与胆汁酸结合形成牛黄胆酸,牛磺胆酸对消化道中脂类的吸收是必需的。
------------是不是脂类少的话牛黄胆酸就不需要那么多会产生的少点?




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